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Haematologica. 2012 Mar;97(3):437-41. doi: 10.3324/haematol.2011.060129. Epub 2011 Dec 29.

NOTCH1 mutations in +12 chronic lymphocytic leukemia (CLL) confer an unfavorable prognosis, induce a distinctive transcriptional profiling and refine the intermediate prognosis of +12 CLL.

Author information

1
Division of Hematology, Department of Cellular Biotechnologies and Haematology University, Sapienza Via Benevento 6, 00161 Rome, Italy. delgiudice@bce.uniroma1.it

Abstract

Trisomy 12, the third most frequent chromosomal aberration in chronic lymphocytic leukemia (CLL), confers an intermediate prognosis. In our cohort of 104 untreated patients carrying +12, NOTCH1 mutations occurred in 24% of cases and were associated to unmutated IGHV genes (P=0.003) and +12 as a sole cytogenetic abnormality (P=0.008). NOTCH1 mutations in +12 CLL associated with an approximately 2.4 fold increase in the risk of death, a significant shortening of survival (P<0.01) and proved to be an independent predictor of survival in multivariate analysis. Analogous to +12 CLL with TP53 disruption or del(11q), NOTCH1 mutations in +12 CLL conferred a significantly worse survival compared to that of +12 CLL with del(13q) or +12 only. The overrepresentation of cell cycle/proliferation related genes of +12 CLL with NOTCH1 mutations suggests the biological contribution of NOTCH1 mutations to determine a poor outcome. NOTCH1 mutations refine the intermediate prognosis of +12 CLL.

PMID:
22207691
PMCID:
PMC3291600
DOI:
10.3324/haematol.2011.060129
[Indexed for MEDLINE]
Free PMC Article

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